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Jordi Garcia-Ojalvo

Publications and source records attributed to Jordi Garcia-Ojalvo.

At least 19 recordsLinked to original sources

Determinants of hyperparameter robustness in connectome reservoir computing

Reservoir computing provides a controlled setting for studying how recurrent network architectureshapes computation: input signals are projected into a high-dimensional state space by a fixed nonlinear dynamical system, and only the readout is trained. However, reservoir performance can be dependent on hyperparameters; this paper asks which recurrent network features support robustness to those parameter changes. We characterize computational performance using memory capacity (MC), truncated single-delay information-processing capacity (IPC), and kernel rank (KR). Generalization across input histories is measured using generalization rank (GR), while hyperparameter robustness is quantified using the coefficient of variation (CV) of each metric across sweeps of target spectral radius, input scaling, leak rate, and neuron bias. To examine the architectural determinants of robustness, we construct perturbations that alter connectivity topology, excitatory/inhibitory sign structure, weight magnitudes, and weight placement while preserving complementary properties. Across these experiments, the C. elegans connectome consistently occupies a relatively low-variance regime. The central result is a performance-robustness tradeoff: architecture variants with higher task-agnostic performance also tend to exhibit greater hyperparameter sensitivity and poorer common-tail generalization. Across the E/I edge balance sweeps and shuffle controls, this tradeoff is closely associated with the raw spectral radius before normalization. Because every perturbed matrix is rescaled to the same target radius, matrices with lower raw spectral radius receive greater global amplification of their recurrent weights. The observed differences among architectures therefore characterize the joint effects of structural variation and architecture-specific global rescaling under spectral-radius normalization.

q-bio.NC↗

Rosetta Stone of Neural Mass Models

Brain dynamics dominate every level of neural organization -- from single-neuron spiking to the macroscopic waves captured by functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and electroencephalography (EEG) -- yet the mathematical tools used to interrogate those dynamics remain scattered across a patchwork of traditions. Neural mass models (NMMs) (aggregate neural models) provide one of the most popular gateways into this landscape, but their sheer variety -- spanning lumped parameter models, firing-rate equations, and multi-layer generators -- demands a unifying framework that situates diverse architectures along a continuum of abstraction and biological detail. Here, we start from the idea that oscillations originate from a simple push-pull interaction between two or more neural populations. We build from the undamped harmonic oscillator and, guided by a simple push-pull motif between excitatory and inhibitory populations, climb a systematic ladder of detail. Each rung is presented first in isolation, next under forcing, and then within a coupled network, reflecting the progression from single-node to whole-brain modeling. By transforming a repertoire of disparate formalisms into a navigable ladder, we hope to turn NMM choice from a subjective act into a principled design decision, helping both theorists and experimentalists translate between scales, modalities, and interventions. In doing so, we offer a Rosetta Stone for brain oscillation models -- one that lets the field speak a common dynamical language while preserving the dialectical richness that fuels discovery.

q-bio.NC↗

Mapping gene expression dynamics to developmental phenotypes with information entropy analysis

The development of multicellular organisms entails a deep connection between time-dependent biochemical processes taking place at the subcellular level, and the resulting macroscopic phenotypes that arise in populations of up to trillions of cells. A statistical mechanics of developmental processes would help to understand how microscopic genotypes map onto macroscopic phenotypes, a general goal across biology. Here we follow this approach, hypothesizing that development should be understood as a thermodynamic transition between non-equilibrium states. We test this hypothesis in the context of the fruit fly, Drosophila melanogaster, a model organism used widely in genetics and developmental biology for over a century. Applying a variety of information-theoretic measures to public transcriptomics datasets of whole fly embryos during development, we show that the global temporal dynamics of gene expression can be understood as a process that probabilistically guides embryonic dynamics across macroscopic phenotypic stages. In particular, we demonstrate signatures of irreversibility in the information complexity of transcriptomic dynamics, as measured mainly by the permutation entropy of indexed ensembles (PI entropy). Our results show that the dynamics of PI entropy correlate strongly with developmental stages. Overall, this is a test case in applying information complexity analysis to relate the statistical mechanics of biomarkers to macroscopic developmental dynamics.

physics.bio-ph↗

Reinforcement learning in densely recurrent biological networks

Training highly recurrent networks in continuous action spaces is a technical challenge: gradient-based methods suffer from exploding or vanishing gradients, while purely evolutionary searches converge slowly in high-dimensional weight spaces. We introduce a hybrid, derivative-free optimization framework that implements reinforcement learning by coupling global evolutionary exploration with local direct search exploitation. The method, termed ENOMAD (Evolutionary Nonlinear Optimization with Mesh Adaptive Direct search), is benchmarked on a suite of food-foraging tasks instantiated in the fully mapped neural connectome of the nematode \emph{Caenorhabditis elegans}. Crucially, ENOMAD leverages biologically derived weight priors, letting it refine--rather than rebuild--the organism's native circuitry. Two algorithmic variants of the method are introduced, which lead to either small distributed adjustments of many weights, or larger changes on a limited number of weights. Both variants significantly exceed the performance of the untrained connectome (in what can be interpreted as an example of transfer learning) and of existing training strategies. These findings demonstrate that integrating evolutionary search with nonlinear optimization provides an efficient, biologically grounded strategy for specializing natural recurrent networks towards a specified set of tasks.

cs.NE↗

Structural determinants of soft memory in recurrent biological networks

Recurrent neural networks are frequently studied in terms of their information-processing capabilities. The structural properties of these networks are seldom considered, beyond those emerging from the connectivity tuning necessary for network training. However, real biological networks have non-contingent architectures that have been shaped by evolution over eons, constrained partly by information-processing criteria, but more generally by fitness maximization requirements. Here we examine the topological properties of existing biological networks, focusing in particular on gene regulatory networks in bacteria. We identify structural features, both local and global, that dictate the ability of recurrent networks to store information on the fly and process complex time-dependent inputs.

q-bio.MN↗

Role of connectivity anisotropies in the dynamics of cultured neuronal networks

Laboratory-grown, engineered living neuronal networks in vitro have emerged in the last years as an experimental technique to understand the collective behavior of neuronal assemblies in relation to their underlying connectivity. An inherent obstacle in the design of such engineered systems is the difficulty to predict the dynamic repertoire of the emerging network and its dependence on experimental variables. To fill this gap, and inspired on recent experimental studies, here we present a numerical model that aims at, first, replicating the anisotropies in connectivity imprinted through engineering, to next realize the collective behavior of the neuronal network and make predictions. We use experimentally measured, biologically-realistic data combined with the Izhikevich model to quantify the dynamics of the neuronal network in relation to tunable structural and dynamical parameters. These parameters include the synaptic noise, strength of the imprinted anisotropies, and average axon lengths. The latter are involved in the simulation of the development of neurons in vitro. We show that the model captures the behavior of engineered neuronal cultures, in which a rich repertoire of activity patterns emerge but whose details are strongly dependent on connectivity details and noise. Results also show that the presence of connectivity anisotropies substantially improves the capacity of reconstructing structural connectivity from activity data, an aspect that is important in the quest for understanding the structure-to-function relationship in neuronal networks. Our work provides the in silico basis to assist experimentalists in the design of laboratory in vitro networks and anticipate their outcome, an aspect that is particularly important in the effort to conceive reliable brain-on-a-chip circuits and explore key aspects such as input-output relationships or information coding.

q-bio.NC↗

From chimeras to extensive chaos in networks of heterogeneous Kuramoto oscillator populations

Populations of coupled oscillators can exhibit a wide range of complex dynamical behavior, from complete synchronization to chimera and chaotic states. We can thus expect complex dynamics to arise in networks of such populations. Here we analyze the dynamics of networks of populations of heterogeneous mean-field coupled Kuramoto-Sakaguchi oscillators, and show that the instability that leads to chimera states in a simple two-population model also leads to extensive chaos in large networks of coupled populations. Formally, the system consists of a complex network of oscillator populations whose mesoscopic behavior evolves according to the Ott-Antonsen equations. By considering identical parameters across populations, the system contains a manifold of homogeneous solutions where all populations behave identically. Stability analysis of these homogeneous states provided by the master stability function formalism shows that non-trivial dynamics might emerge on a wide region of the parameter space for arbitrary network topologies. As examples, we first revisit the two-population case, and provide a complete bifurcation diagram. Then, we investigate the emergent dynamics in large ring and Erdös-Rényi networks. In both cases, transverse instabilities lead to extensive space-time chaos, i.e., irregular regimes whose complexity scales linearly with the system size. Our work provides a unified analytical framework to understand the emergent dynamics of networks of oscillator populations, from chimera states to robust high-dimensional chaos.

nlin.CD↗

Network-community analysis of cellular senescence

Most cellular phenotypes are genetically complex. Identifying the set of genes that are most closely associated with a specific cellular state is still an open question in many cases. Here we study the transcriptional profile of cellular senescence using a combination of network-based approaches, which include eigenvector centrality feature selection and community detection. We apply our method to cell-type-resolved RNA sequencing data obtained from injured muscle tissue in mice. The analysis identifies some genetic markers consistent with previous findings, and other previously unidentified ones, which are validated with previously published single-cell RNA sequencing data in a different type of tissue. The key identified genes, both those previously known and the newly identified ones, are transcriptional targets of factors known to be associated with established hallmarks of senescence, and can thus be interpreted as molecular correlates of such hallmarks. The method proposed here could be applied to any complex cellular phenotype even when only bulk RNA sequencing is available, provided the data is resolved by cell type.

q-bio.QM↗

Biological computation through recurrence

One of the defining features of living systems is their adaptability to changing environmental conditions. This requires organisms to extract temporal and spatial features of their environment, and use that information to compute the appropriate response. In the last two decades, a growing body or work, mainly coming from the machine learning and computational neuroscience fields, has shown that such complex information processing can be performed by recurrent networks. In those networks, temporal computations emerge from the interaction between incoming stimuli and the internal dynamic state of the network. In this article we review our current understanding of how recurrent networks can be used by biological systems, from cells to brains, for complex information processing. Rather than focusing on sophisticated, artificial recurrent architectures such as long short-term memory (LSTM) networks, here we concentrate on simpler network structures and learning algorithms that can be expected to have been found by evolution. We also review studies showing evidence of naturally occurring recurrent networks in living organisms. Lastly, we discuss some relevant evolutionary aspects concerning the emergence of this natural computation paradigm.

q-bio.NC↗

A multiscale sensorimotor model of experience-dependent behavior in a minimal organism

To survive in ever-changing environments, living organisms need to continuously combine the ongoing external inputs they receive, representing present conditions, with their dynamical internal state, which includes influences of past experiences. It is still unclear in general, however, (i) how this happens at the molecular and cellular levels, and (ii) how the corresponding molecular and cellular processes are integrated with the behavioral responses of the organism. Here we address these issues by modeling mathematically a particular behavioral paradigm in a minimal model organism, namely chemotaxis in the nematode C. elegans. Specifically, we use a long-standing collection of elegant experiments on salt chemotaxis in this animal, in which the migration direction varies depending on its previous experience. Our model integrates the molecular, cellular and organismal levels to reproduce the experimentally observed experience-dependent behavior. The model proposes specific molecular mechanisms for the encoding of current conditions and past experiences in key neurons associated with this response, predicting the behavior of various mutants associated with those molecular circuits.

q-bio.NC↗

Parametric modeling of mechanical effects on circadian oscillators

Circadian rhythms are archetypical examples of nonlinear oscillations. While these oscillations are usually attributed to circuits of biochemical interactions among clock genes and proteins, recent experimental studies reveal that they are also affected by the cell's mechanical environment. Here we extend a standard biochemical model of circadian rhythmicity to include mechanical effects in a parametric manner. Using experimental observations to constrain the model, we suggest specific ways in which the mechanical signal might affect the clock. Additionally, a bifurcation analysis of the system predicts that these mechanical signals need to be within an optimal range for circadian oscillations to occur.

q-bio.CB↗

Single-cell Bayesian deconvolution

Individual cells exhibit substantial heterogeneity in protein abundance and activity, which is frequently reflected in broad distributions of fluorescently labeled reporters. Since all cellular components are intrinsically fluorescent to some extent, the observed distributions contain background noise that masks the natural heterogeneity of cellular populations. This limits our ability to characterize cell-fate decision processes that are key for development, immune response, tissue homeostasis, and many other biological functions. It is therefore important to separate the contributions from signal and noise in single-cell measurements. Addressing this issue rigorously requires deconvolving the noise distribution from the signal, but approaches in that direction are still limited. Here we present a non-parametric Bayesian formalism that performs such a deconvolution efficiently on multidimensional measurements, in a way that allows estimating confidence intervals precisely. We use the approach to study the expression of the mesodermal transcription factor Brachyury in mouse embryonic stem cells undergoing differentiation.

q-bio.QM↗

Comparison between an exact and a heuristic neural mass model with second order synapses

Neural mass models (NMMs) are designed to reproduce the collective dynamics of neuronal populations. A common framework for NMMs assumes heuristically that the output firing rate of a neural population can be described by a static nonlinear transfer function (NMM1). However, a recent exact mean-field theory for quadratic integrate-and-fire (QIF) neurons challenges this view by showing that the mean firing rate is not a static function of the neuronal state but follows two coupled nonlinear differential equations (NMM2). Here we analyze and compare these two descriptions in the presence of second-order synaptic dynamics. First, we derive the mathematical equivalence between the two models in the infinitely slow synapse limit, i.e., we show that NMM1 is an approximation of NMM2 in this regime. Next, we evaluate the applicability of this limit in the context of realistic physiological parameter values by analyzing the dynamics of models with inhibitory or excitatory synapses. We show that NMM1 fails to reproduce important dynamical features of the exact model, such as the self-sustained oscillations of an inhibitory interneuron QIF network. Furthermore, in the exact model but not in the limit one, stimulation of a pyramidal cell population induces resonant oscillatory activity whose peak frequency and amplitude increase with the self-coupling gain and the external excitatory input. This may play a role in the enhanced response of densely connected networks to weak uniform inputs, such as the electric fields produced by non-invasive brain stimulation.

q-bio.NC↗

Signaling oscillations: molecular mechanisms and functional roles

Mounting evidence shows that oscillatory activity is widespread in cell signaling. Here we review some of this recent evidence, focusing on both the molecular mechanisms that potentially underlie such dynamical behavior, and the potential advantages that signaling oscillations might have in cell function. The biological processes considered include tissue maintenance, embryonic development and wound healing. With the aid of mathematical modeling, we show that a common principle, namely delayed negative feedback, underpins this wide variety of phenomena.

q-bio.CB↗

Mechanistic models of cell-fate transitions from single-cell data

Our knowledge of how individual cells self-organize to form complex multicellular systems is being revolutionized by a data outburst, coming from high-throughput experimental breakthroughs such as single-cell RNA sequencing and spatially resolved single-molecule FISH. This information is starting to be leveraged by machine learning approaches that are helping us establish a census and timeline of cell types in developing organisms, shedding light on how biochemistry regulates cell-fate decisions. In parallel, imaging tools such as light-sheet microscopy are revealing how cells self-assemble in space and time as the organism forms, thereby elucidating the role of cell mechanics in development. Here we argue that mathematical modeling can bring together these two perspectives, by enabling us to test hypotheses about specific mechanisms, which can be further validated experimentally. We review the recent literature on this subject, focusing on representative examples that use modeling to better understand how single-cell behavior shapes multicellular organisms.

q-bio.CB↗

A tunable population timer in multicellular consortia

Processing time-dependent information requires cells to quantify the duration of past regulatory events and program the time span of future signals. At the single-cell level, timer mechanisms can be implemented with genetic circuits: sets of genes connected to achieve specific tasks. However, such systems are difficult to implement in single cells due to saturation in molecular components and stochasticity in the limited intracellular space. Multicellular implementations, on the other hand, outsource some of the components of information-processing circuits to the extracellular space, and thereby might escape those constraints. Here we develop a theoretical framework, based on a trilinear coordinate representation, to study the collective behavior of a cellular population composed of three cell types under stationary conditions. This framework reveals that distributing different processes (in our case the production, detection and degradation of a time-encoding signal) across distinct cell types enables the robust implementation of a multicellular timer. Our analysis also shows the circuit to be easily tunable by varying the cellular composition of the consortium.

q-bio.MN↗

Soft-wired long-term memory in a natural recurrent neuronal network

Neuronal networks provide living organisms with the ability to process information. They are also characterized by abundant recurrent connections, which give rise to strong feedback that dictates their dynamics and endows them with fading (short-term) memory. The role of recurrence in long-term memory, on the other hand, is still unclear. Here we use the neuronal network of the roundworm C. elegans to show that recurrent architectures in living organisms can exhibit long-term memory without relying on specific hard-wired modules. A genetic algorithm reveals that the experimentally observed dynamics of the worm's neuronal network exhibits maximal complexity (as measured by permutation entropy). In that complex regime, the response of the system to repeated presentations of a time-varying stimulus reveals a consistent behavior that can be interpreted as soft-wired long-term memory.

q-bio.NC↗

Metabolic basis of brain-like electrical signalling in bacterial communities

Information processing in the mammalian brain relies on a careful regulation of the membrane potential dynamics of its constituent neurons, which propagates across the neuronal tissue via electrical signalling. We recently reported the existence of electrical signalling in a much simpler organism, the bacterium Bacillus subtilis. In dense bacterial communities known as biofilms, nutrient-deprived B. subtilis cells in the interior of the colony use electrical communication to transmit stress signals to the periphery, which interfere with the growth of peripheral cells and reduce nutrient consumption, thereby relieving stress from the interior. Here we explicitly address the interplay between metabolism and electrophysiology in bacterial biofilms, by introducing a spatially-extended mathematical model that combines the metabolic and electrical components of the phenomenon in a discretised reaction-diffusion scheme. The model is experimentally validated by environmental and genetic perturbations, and confirms that metabolic stress is transmitted through the bacterial population via a potassium wave. Interestingly, this behaviour is reminiscent of cortical spreading depression in the brain, characterised by a wave of electrical activity mediated by potassium diffusion that has been linked to various neurological disorders, calling for future studies on the evolutionary link between the two phenomena.

q-bio.NC↗